Although most carcinoens or their metabolites have been shown to be mutagenic in a variety of systems, the relationship between mutagenicity and carcinogenicity is not clear. The finding that damage to DNA by chemical carcinogens results in DNA repair led to the concept that error-prone repair may be a key feature of both mutagenesis and carcinogenesis. A better understanding of mutagenesis resulting from damage to DNA is therefore fundamental to our understanding of the mechanism of chemical carcinogenesis. Standard methods for the study of DNA repair measure only the extent of repair, not the fidelity of repair, which is probably the factor leading to most biological consequences. Fidelity can best be studied by studying the mutation rate after a given amount of damage to the DNA. The proposed research seeks to identify the mutagenic (error-prone) modes of DNA repair in cultured cells exposed to UV light and chemical carcinogens, and to determine how error-prone pathways are controlled by genetic, physiological and pharmacological factors. Ongoing research on the nature of error-prone repair in E. coli, and the effects of heavy metals on this repair, shall be continued and extended to cell culture systems. Test systems to detect agents which affect error-prone repair levels will be developed to screen for cocarcinogens which may not be mutagenic per se. Changes in the mutation rate after a standard amount of damage to the DNA by UV light will reflect the proportion of DNA which is error-prone. This test system could also lead to the discovery of safe antimutagens which would be useful in cancer chemotherapy or prevention.